Skip to main content

Advertisement

SpringerLink
Log in

Influence of diet and body weight in treatment-resistant acquired partial lipodystrophy after hematopoietic stem cell transplantation and its potential for metabolic improvement

  • Case Report
  • Published:
Diabetology International Aims and scope Submit manuscript

Abstract

Lipodystrophy is a rare disease characterized by various metabolic complications resulting from the complete or partial loss of adipose tissues and abnormal fat accumulation. Acquired lipodystrophy may occur due to certain drugs, autoimmunity or for unknown reasons. Recently, cases of acquired lipodystrophy after hematopoietic stem cell transplantation (HSCT) have been reported. Leptin administration, used recently to treat generalized lipodystrophy, effectively controlled metabolic complications; however, few reports demonstrated the effectiveness of leptin for acquired partial lipodystrophy. In this report, we present the case of a 17-year-old woman who developed insulin resistance, hypertriglyceridemia, and fatty liver after HSCT. Due to her thin gluteal fat and low blood adiponectin levels, her metabolic abnormalities were attributed to partial lipodystrophy. While both leptin and pemafibrate administration partially attenuated metabolic abnormalities, its effects were relatively limited, probably because the serum leptin levels were maintained, which is not likely in generalized lipodystrophy. Nevertheless, after she developed adjustment disorder and experienced weight loss, along with decreased food intake, her metabolic markers significantly improved. This case suggests the modest effect of leptin and permafibrate in partial lipodystrophy after HSCT, highlighting the importance of diet therapy in metreleptin treatment for acquired partial lipodystrophy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

All the data supporting our findings is available from corresponding author upon request.

References

  1. Brown RJ, Araujo-Vilar D, Cheung PT, Dunger D, Garg A, Jack M, et al. The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline. J Clin Endocrinol Metab. 2016;101:4500–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Özen S, Akıncı B, Oral EA. Current diagnosis, treatment and clinical challenges in the management of lipodystrophy syndromes in children and young people. J Clin Res Pediatr Endocrinol. 2020;12:17–28.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Vigouroux C, Guénantin AC, Vatier C, Capel E, Le Dour C, Afonso P, et al. Lipodystrophic syndromes due to LMNA mutations: recent developments on biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives. Nucleus. 2018;9:235–48.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kobayashi N, Nakahara M, Oka M, Saeki K. Additional attention to combination antiretroviral therapy-related lipodystrophy. World J Virol. 2017;6:49–52.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Falcao CK, Cabral MCS, Mota JM, Arbache ST, Costa-Riquetto AD, Muniz DQB, et al. Acquired lipodystrophy associated with nivolumab in a patient with advanced renal cell carcinoma. J Clin Endocrinol Metab. 2019;104:3245–8.

    Article  PubMed  Google Scholar 

  6. Smedmyr B, Wibell L, Simonsson B, Oberg G. Impaired glucose tolerance after autologous bone marrow transplantation. Bone Marrow Transplant. 1990;6:89–92.

    CAS  PubMed  Google Scholar 

  7. Taskinen M, Saarinen-Pihkala UM, Hovi L, Lipsanen-Nyman M. Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Lancet. 2000;356:993–7.

    Article  CAS  PubMed  Google Scholar 

  8. Lorini R, Cortona L, Scaramuzza A, De Stefano P, Locatelli F, Bonetti F, et al. Hyperinsulinemia in children and adolescents after bone marrow transplantation. Bone Marrow Transplant. 1995;15:873–7.

    CAS  PubMed  Google Scholar 

  9. Wei C, Thyagiarajan MS, Hunt LP, Shield JP, Stevens MC, Crowne EC. Reduced insulin sensitivity in childhood survivors of haematopoietic stem cell transplantation is associated with lipodystropic and sarcopenic phenotypes. Pediatr Blood Cancer. 2015;62:1992–9.

    Article  CAS  PubMed  Google Scholar 

  10. Bizzarri C, Pinto RM, Ciccone S, Brescia LP, Locatelli F, Cappa M. Early and progressive insulin resistance in young, non-obese cancer survivors treated with hematopoietic stem cell transplantation. Pediatr Blood Cancer. 2015;62:1650–5.

    Article  CAS  PubMed  Google Scholar 

  11. Adachi M, Asakura Y, Muroya K, Goto H, Kigasawa H. Abnormal adipose tissue distribution with unfavorable metabolic profile in five children following hematopoietic stem cell transplantation: a new etiology for acquired partial lipodystrophy. Clin Pediatr Endocrinol. 2013;22:53–64.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Diker-Cohen T, Cochran E, Gorden P, Brown RJ. Partial and generalized lipodystrophy: comparison of baseline characteristics and response to Metreleptin. J Clin Endocrinol Metab. 2015;100:1802–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fiorenza CG, Chou SH, Mantzoros CS. Lipodystrophy: pathophysiology and advances in treatment. Nat Rev Endocrinol. 2011;7:137–50.

    Article  CAS  PubMed  Google Scholar 

  14. Nagayama A, Ashida K, Moritaka K, Hidaka M, Gobaru M, Tanaka S, et al. Metreleptin supplementation for improving lipid and glycemic profiles in acquired diabetes lipodystrophy: a case report. J Endocr Soc. 2019;3:2179–83.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Adachi M, Muroya K, Hanakawa J, Asakura Y. Metreleptin worked in a diabetic woman with a history of hematopoietic stem cell transplantation (HSCT) during infancy: further support for the concept of’HSCT-associated lipodystrophy. Endocr J. 2021;68:399–407.

    Article  CAS  PubMed  Google Scholar 

  16. Japan: The National Statistic Center. Portal Site of Official Statistics of Japan. http://e-stat.go.jp. (in Japanese). 2017. Accessed 12 Nov 2020.

  17. Shibata Y, Nakatsuka A, Eguchi J, Miyamoto S, Masuda Y, Awazawa M, et al. Acquired partial lipoatrophy as graft-versus-host disease and treatment with metreleptin: two case reports. J Med Case Rep. 2018;12:368.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Nagayama A, Ashida K, Watanabe M, Moritaka K, Sonezaki A, Kitajima Y, et al. Case report: metreleptin and SGLT2 inhibitor combination therapy is effective for acquired incomplete lipodystrophy. Front Endocrinol (Lausanne). 2021;12: 690996.

    Article  PubMed  Google Scholar 

  19. Bamba V. Update on screening, etiology, and treatment of dyslipidemia in children. J Clin Endocrinol Metab. 2014;99:3093–102.

    Article  CAS  PubMed  Google Scholar 

  20. Lorenc A, Hamilton-Shield J, Perry R, Stevens M, group CHAaMLEW. Body composition after allogeneic haematopoietic cell transplantation/total body irradiation in children and young people: a restricted systematic review. J Cancer Surviv. 2020;14:624–42.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zammouri J, Vatier C, Capel E, Auclair M, Storey-London C, Bismuth E, et al. Molecular and cellular bases of lipodystrophy syndromes. Front Endocrinol (Lausanne). 2021;12: 803189.

    Article  PubMed  Google Scholar 

  22. Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman RA, Briggs M, Deeb S, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 1996;15:5336–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yamashita S, Masuda D, Matsuzawa Y. Pemafibrate, a new selective PPARα modulator: drug concept and its clinical applications for dyslipidemia and metabolic diseases. Curr Atheroscler Rep. 2020;22:5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Arai H, Yamashita S, Yokote K, Araki E, Suganami H, Ishibashi S, et al. Efficacy and safety of pemafibrate versus fenofibrate in patients with high triglyceride and low HDL cholesterol levels: a multicenter, placebo-controlled, double-blind, randomized trial. J Atheroscler Thromb. 2018;25:521–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Baykal AP, Parks EJ, Shamburek R, Syed-Abdul MM, Chacko S, Cochran E, et al. Leptin decreases de novo lipogenesis in patients with lipodystrophy. JCI Insight. 2020;5: e137180.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Unger RH, Roth MG. A new biology of diabetes revealed by leptin. Cell Metab. 2015;21:15–20.

    Article  CAS  PubMed  Google Scholar 

  27. Moran SA, Patten N, Young JR, Cochran E, Sebring N, Reynolds J, et al. Changes in body composition in patients with severe lipodystrophy after leptin replacement therapy. Metabolism. 2004;53:513–9.

    Article  CAS  PubMed  Google Scholar 

  28. Aotani D, Ebihara K, Sawamoto N, Kusakabe T, Aizawa-Abe M, Kataoka S, et al. Functional magnetic resonance imaging analysis of food-related brain activity in patients with lipodystrophy undergoing leptin replacement therapy. J Clin Endocrinol Metab. 2012;97:3663–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, et al. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature. 2010;464:1313–9.

    Article  CAS  PubMed  Google Scholar 

  30. Hashimoto H, Yamamoto M, Sugiura E, Abe H, Kagawa T, Goto M, et al. Adiponectin deficiency-induced diabetes increases TNFα and FFA via downregulation of PPARα. J Vet Med Sci. 2018;80:662–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Robbins DC, Danforth EJ Jr, Horton ES, Burse RL, Goldman RF, Sims EA. The effect of diet on thermogenesis in acquired lipodystrophy. Metabolism. 1979;28:908–16.

    Article  CAS  PubMed  Google Scholar 

  32. Koo E, Foss-Freitas MC, Meral R, Ozer M, Eldin AJ, Akinci B, et al. The metabolic equivalent BMI in patients with familial partial lipodystrophy (FPLD) compared with those with severe obesity. Obesity (Silver Spring). 2021;29:274–8.

    Article  PubMed  Google Scholar 

  33. Tanaka T, Kusakabe T, Ebihara K, Aizawa-Abe M, Aotani D, Yorifuji T, et al. Practice guideline for lipodystrophy syndromes-clinically important diseases of the Japan Endocrine Society (JES). Endocr J. 2021;68:1027–42.

    Article  CAS  PubMed  Google Scholar 

  34. Nomura H, Son C, Aotani D, Shimizu Y, Katsuura G, Noguchi M, et al. Impaired leptin responsiveness in the nucleus accumbens of leptin-overexpressing transgenic mice with dysregulated sucrose and lipid preference independent of obesity. Neurosci Res. 2022;177:94–102.

    Article  CAS  PubMed  Google Scholar 

  35. Suyama S, Maekawa F, Maejima Y, Kubota N, Kadowaki T, Yada T. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. Sci Rep. 2016;6:30796.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Baker KS, Chow EJ, Goodman PJ, Leisenring WM, Dietz AC, Perkins JL, et al. Impact of treatment exposures on cardiovascular risk and insulin resistance in childhood cancer survivors. Cancer Epidemiol Biomark Prev. 2013;22:1954–63.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr. Ken Ebihara of Jichi Medical University for great suggestions about the diagnosis and treatment of secondary partial lipodystrophy after HSCT.

This work was not supported by any grant.

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Gunma University Graduate School of Medicine, 3-39-15 Showa-Machi, Maebashi, Gunma, 371-8511, Japan

    Emi Ishida, Kazuhiko Horiguchi, Shunichi Matsumoto, Atsushi Ozawa, Sho Sekiguchi & Eijiro Yamada

Authors
  1. Emi Ishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuhiko Horiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shunichi Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Atsushi Ozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sho Sekiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eijiro Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emi Ishida.

Ethics declarations

Conflict of interest

None of the authors have any potential conflicts of interest associated with this report.

Human rights statement and informed consent

All procedures followed were in accordance with the Helsinki Declaration of 1964 and later versions. Informed consent for it was obtained from the patient and her parent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ishida, E., Horiguchi, K., Matsumoto, S. et al. Influence of diet and body weight in treatment-resistant acquired partial lipodystrophy after hematopoietic stem cell transplantation and its potential for metabolic improvement. Diabetol Int 15, 290–296 (2024). https://doi.org/10.1007/s13340-023-00674-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13340-023-00674-6

Keywords

Search

Navigation